Asymptomatic cerebral small infarcts (lacunae), their risk factors and intellectual disturbances.

This study examines the relationship between cerebral small infarcts (lacunae) and the multiple risk factors of diabetes, age, hypertension, hyperlipidemia, and atherosclerosis in asymptomatic NIDDM patients and nondiabetic subjects by comparing brain magnetic resonance imaging (MRI) findings to these risk factors. Brain MRI was performed on 155 asymptomatic NIDDM and 39 asymptomatic nondiabetic patients, using a Shimazu SMT-150, 1.5-T instrument. Among the diabetic patients, 65 showed evidence of lacunae. The incidence of lacunae was significantly higher in older diabetic patients, but it did not significantly differ in those with or without the risk factors of atherosclerosis. We also correlated the results of a freehand cube-drawing test with the incidence of lacunae. Cube-drawing is a good indicator of spatial cognition ability supported by wide association areas of the brain. Drawing ability was tested in 56 diabetic and 39 nondiabetic subjects. Correlations of lacuna incidence with deformity in drawing and with age were high in the diabetic group. Correlation of lacunae with deformity in drawing was also significant in nondiabetic subjects. The incidence of lacunae was highly correlated with intellectual impairment.

3,3',5'-triiodothyronine (reverse T3) in human cerebrospinal fluid.

To examine the metabolic products of thyroid hormones in the central nervous system, total and free rT3 as well as T4 in human cerebrospinal fluid (CSF) were determined in 41 patients. Total T4, T3, and rT3 concentrations in CSF were determined by RIA, and free T4, T3, and rT3 fractions were analyzed by the magnesium precipitation method. The mean (+/- SE) total T4 and T3 concentrations in CSF were 166 +/- 24 and 2.6 +/- 1.5 ng/dl, respectively; the values were approximatey 2% of those in normal control pooled sera. Total rT3 concentrations in CSF from 29 clinically euthyroid patients who were apparently in a normal nutritional state ranged from 5.2-23 ng/dl (mean +/- SE, 11.2 +/- 0.9 ng/dl); the value was approximately 40% of that in sera. A patient with primary hypothyroidism had a markedly diminished CSF rT3 concentration (1.1 ng/dl), and the remaining 11 patients, suffering from severe diseases such as meningitis and cerebrovascular accident, had significantly higher CSF rT3 concentrations (37.5 +/- 6.6 ng/dl) than the clinically euthyroid patients. Although free T4 and T3 concentrations in CSF (5.9 +/- 1.1 and 0.16 +/- 0.05 ng/dl, respectively) were similar to those in serum (2.1 +/- 0.2 and 0.22 +/- 0.01 ng/dl, respectively), the free rT3 concentration in CSF (0.70 +/- 0.12 ng/dl) was approximately 20 times higher than that (0.044 +/- 0.016 ng/dl) in serum. Furthermore, the reciprocal relationship was observed between CSF total rT3 concentrations and free rT3 percentages in CSF. These data suggest the possibility that rT3 may be produced from T4 in human brain and that there may be a transport mechanism regulating free rT3 in CSF.

Pathologic laughing and crying treated with levodopa.

Levodopa or amantadine hydrochloride was administered to 25 patients with pathologic laughing and/or crying. This symptom was markedly improved in ten cases, most of which were devoid of a cortical atrophy or a periventricular lucency in computed tomographic scan and also devoid of a severe dementia or a disturbance in activity of daily living. The concentration of homovanillic acid in the CSF of the patients was significantly decreased, whereas the concentration of 5-hydroxyindoleacetic acid remained within the normal limit. Because part of pathologic laughing and crying seems to be caused by the decreased function of the dopaminergic neuron, levodopa or amantadine is worth trying.

Genetic studies in Parkinson's disease with an alpha-synuclein/NACP gene polymorphism in Japan.

Dinucleotide repeat polymorphism has been observed in the promoter of the alpha-synuclein (alpha-SYN)/NAC precursor protein (NACP) gene. Alpha-SYN/NACP allele 3 (described by Xia et al. (Ann. Neurol., 40 (1996) 207), equivalent to allele 1 described by Krüger et al. (Ann. Neurol. 45 (1999) 611) is reported to be significantly more frequent among patients with sporadic Parkinson's disease (sPD) than controls. In this study, we genotyped the same alpha-SYN/NACP polymorphism in Japanese sPD patients and healthy controls, but found that any aliele showed no significant difference between the two groups.

Diabetes mellitus and cerebral vascular disease.

Non-fatal or small infarction, especially with multiple occurrence, is a feature of cerebrovascular disease complicating diabetes mellitus. The atherosclerosis of the cervical and cerebral arteries, especially in the posterior circulation, in diabetes is more severe than that in non-diabetics. We reviewed the incidence of vascular lesions, and clinical history in 25 male and 26 female diabetic autopsy subjects. In addition, the long-term effects of blood pressure and glucose values were evaluated in 267 stroke patients without cerebral embolism, 99 of whom had diabetes mellitus. Asymptomatic cerebral infarction is not rare in diabetic subjects, and can now be accurately pathologically and clinically evaluated using MRI. The results of our study indicate that high blood pressure and poor blood glucose control are associated with the higher incidence of cerebral infarction in the diabetic patients.

Asymptomatic multiple lacunae in diabetics and non-diabetics detected by brain magnetic resonance imaging.

We investigated the relationship between asymptomatic multiple lacunae (ASML) and related risk factors by using brain MRI in 209 patients including 152 NIDDM patients. Patients with ASML (97 cases) were significantly older (68 +/- 9 vs. 63 +/- 10) and hypertension was more frequent (57/97 vs. 33/112) than in patients without ASML. In addition, by multivariate analysis, ASML showed significant association with aging and hypertension, but not with NIDDM. In the NIDDM patients, diabetics with ASML were significantly older, and showed a higher association with hypertension and triopathy than those without ASML, although the results were the same for the middle-aged (< 65 years old) diabetics. From multivariate analysis, the lesions in the penetrating branch area were highly associated with hypertension (F = 8.46) and nephropathy (F = 4.75), while those in the subcortex and white matter were associated with aging (F = 6.02) and retinopathy (F = 5.15). In the middle-aged diabetics, the former was associated with hypertension (F = 10.72) and retinopathy (F = 13.32), whereas the latter was associated with retinopathy (F = 20.76). In the elderly diabetics, no significant association was found in either lesions. These results suggest that control of hypertension and prevention of microangiopathy by keeping good control of blood glucose, is essential to prevent asymptomatic lacunae in NIDDM patients.

The changes of lacunar state during a 5-year period in NIDDM.

With the increment of the aged, primary and secondary prevention of cerebrovascular disease in the Japanese diabetics are crucial problems. Early detection of asymptomatic infarction, not rare in diabetics, is important in the view of cost benefits. Little is known about the development and progression of asymptomatic infarction. We investigated the number of lacuna during a period of 5 years in 51 non-insulin-dependent diabetes mellitus (NIDDM). At the initiation of this study, 22 patients were free from lacuna and another 29 patients had asymptomatic multiple lacunae. In the former patients, no risk factors were different between the 13 patients with still no lacuna and the nine patients with lacuna-developed after 5 years. In the latter patients, the 17 patients with worsening lacunar state had significantly higher systolic blood pressure, and a higher prevalence of macroalbuminuria than the 12 patients with no increment of lacuna. Multiple logistic regression analysis showed that macroalbuminuria after 5 years was the only contributing factor to the increased lacuna. Therefore, in the NIDDM, macroalbuminuria induced an increase of lacuna in magnetic resonance imaging, although numbers of cases were relatively small. Prevention of the development of macroalbuminuria are essential to avoid the progression of asymptomatic lacuna.

Subcortical neurofibrillary tangles, neuropil threads, and argentophilic glial inclusions in corticobasal degeneration.

This report concerns an autopsy case of corticobasal degeneration (CBD). The patient was a 64-year-old woman with slowly progressing clumsiness and gait disturbance who died approximately 7 years after the onset of symptoms. The salient neuropathological findings were focal loss of neurons of the cerebral cortex, ballooned neurons and gliosis of the subcortical white matter, thalamus, and basal ganglia. In addition, there were marked neuronal loss and gliosis in the substantia nigra. The ballooned neurons were positively immunostained for phosphorylated neurofilament, alpha B-crystallin and synaptophysin; staining for the latter was intraneuronal. The examination of silver impregnated and Tau immunostained preparations revealed numerous basal neurofibrillary tangles, neuropil threads, and glial inclusions; their presence was most pronounced in the brainstem tegmentum, basal ganglia, and thalamus. Neurofibrillary tangles consisting of straight tubules with a diameter of approximately 13-15 nm and constricted tubules were identified in the substantia nigra. The results of the present study indicate that the cytopathology of the subcortical gray matter and brainstem in CBD patients resembles that of progressive supranuclear palsy.

Asymptomatic lacunes and their relationship to intellectual disturbances.

We studied risk factors and the relationship of lacunes to diabetes mellitus, age, hypertension, hyperlipidemia, atherosclerosis and also to intellectual impairment, comparing brain MRI (magnetic resonance imaging) findings to the multiple risk factors and the results of a cube-handdrawing test. Brain MRI was performed using a Shimazu SMT-150, 1.5 Tesla, in 118 asymptomatic NIDDM and 39 asymptomatic nondiabetic patients. In diabetics, 65 had lacunes and the incidence of lacunes was significantly higher in diabetics with coronary insufficiency by ECG and hypertension, but not significantly different in those with or without the other risk factors. Cube hand-drawing is a good indication of space cognition ability supported by the wide association areas of the brain. Drawing was tested in 41 diabetics and 39 nondiabetics. Correlation of lacunes to deformity in drawing and age was high in both diabetics and nondiabetics. Multiple lacunes were closely related to intellectual impairment.

Deep white matter lesions on MRI, and not silent brain infarcts are related to headache and dizziness of non-specific cause in non-stroke Japanese subjects.

OBJECTIVE: Silent or asymptomatic cerebrovascular disease is believed to be an important risk factor for symptomatic stroke and vascular dementia. Although non-specific complaints such as mild to moderate headache and/or dizziness may also be caused by silent stroke, which remains a topic of controversy. METHODS: To investigate the relationship between silent brain infarcts and non-specific complaints, we assessed findings on magnetic resonance images using a common protocol in the following three groups of subjects; Group 1:78 subjects with non-specific complaints, Group 2:47 subjects with vascular risk factors, and Group 3:75 normal subjects without any subjective complaints or vascular risk factors. In addition to silent stroke, deep white matter lesions on MRI were also evaluated. All subjects were recruited from 12 institutes of the study group located at various parts of Japan. RESULTS: Silent brain infarcts were demonstrated in 44%, 43%, and 20% of subjects in Groups 1, 2, and 3, respectively. In Group 1, the average number of infarcts per individual who had silent brain infarction was 1.8, which was significantly fewer than 3.8 in Group 2 or 3.5 in Group 3 (p<0.0167). White matter lesions were found in 68%, 49%, and 11% in Groups 1, 2, and 3, respectively, indicating that non-specific complaints are more closely related to deep white matter lesions than to silent infarct lesions. Such white matter lesions were found more frequently in subjects with depressive state than in non-depressed subjects (67% vs. 39%, p=0.0155). CONCLUSION: The present results suggest that deep white matter lesions, rather than silent brain infarcts, appear to be important in producing headache and/or dizziness of non-specific cause and also to be related to the depressive state.

[A case of persistent proatlantal intersegmental artery with status epilepticus].

A 48-year-old woman with status epilepticus was admitted to our hospital. On admission, she was comatose with horizontal conjugate deviation of eye balls to the left side. Convulsive seizure of Jacksonian type involved initially the left mouth angle and sequentially the left arm and leg, developing into general convulsion. Routine laboratory examinations revealed no significant abnormality. CT scan was normal but carotid angiogram showed a persistent proatlantal intersegmental artery on the left side. Convulsive seizure lasted five days, followed by left hemiparesis. She recovered completely two weeks later. The origin of her illness remained unclear but the causal relationship between neurological symptoms and the persistent primitive artery was presumed.

[Medial medullary infarction demonstrated by MRI].

A 67-year-old woman with medial medullary infarction is reported, including clinical manifestations, MRI and angiographical findings, and results of evoked potentials. She suffered from contralateral hemiplegia and disturbance of deep sensation. Motor paresis of the tongue was absent. Magnetic resonance imaging revealed a lesion in the medial portion of the medulla oblongata. The 17 cases previously reported with medial medullary infarction are reviewed. Only 3 cases had triad of medial medullary infarction, contralateral hemiparesis, deep sensory disturbance, and ipsilateral hypoglossal paresis. Therefore, lesion detection is necessary to diagnose medial medullary infarction. Most infarctions limited to the upper third of the medulla were caused by occlusions of vertebral arteries or their branches and prognosis was good. In contrast, infarctions in the lower two thirds were caused by occlusions of anterior spinal arteries and their branches and the prognosis was poor. Thus localization of the lesion using MRI plays an important role to predict the prognosis.

[Oncogenic osteomalacic myopathy; a case report].

A 54-year-old man with oncogenic osteomalacic myopathy was reported. He presented with gradual onset of muscle weakness and painful cramp of the bilateral quadriceps femoris muscles, followed by low inorganic phosphorus, elevated alkaline phosphatase in the serum and hyperphosphaturia. The electromyogram (EMG) revealed myogenic change localized in the quadriceps muscle and nerve conduction study was normal. Muscle biopsy of right vastus lateralis muscle demonstrated non-specific myopathic change with minimal neuropathic change: moderate variation in size, many centrally placed nuclei, a few small angulated fibers and pyknotic nuclear clump. The ratio of Type IIA fibers decreased to 5.5%. Serum 25-hydroxyvitamin D and parathormone were normal, whereas 1, 25-dihydroxyvitamin D was above lower normal limit. High dose of 1,25-dihydroxyvitamin D and phosphorus were administered with partial response. CT scan demonstrated tumor in the left 10th rib proximal to the vertebra, invading into the mediastinum. Partial resection of the tumor was performed in order to preserve the rib. Histologically, the tumor was characterized by high vascularity with cystic formation, many giant cells and tumor cells with oval-shaped nuclei. Histopathological diagnosis was primitive mesenchymal tumor (mixed connective tissue variant). Immediately after resecting the tumor, the patient's muscle weakness and painful cramp was prominently relieved and serum inorganic phosphorus and tubular reabsorption of phosphorus became normal, in addition, 1, 25-dihydroxyvitamin D was elevated within normal limit. EMG findings revealed normal motor nerve unit with normal recruitment pattern. Mild myopathy is relatively a common manifestation in patients with osteomalacia. On the other hand, osteomalacia is sometimes caused by tumors, many of which are benign mesenchymal tumors of bone or soft tissue origin.(ABSTRACT TRUNCATED AT 250 WORDS)

[Monocular photopsia preceding with neovascular glaucoma due to internal carotid artery occlusion; a case report].

We described a 67-year-old right handed man with a left internal carotid artery occlusion, who developed monocular photopsia that supervened neovascular glaucoma. He had an antecedent transient motor aphasia. His photopsia, exaggerated by light, persisted intermittently. Orbital bruit was obtained on the left, more clearly during the photopsia. Brain MRI, cerebral angiography, and duplex sonography of carotid and ophthalmic arteries indicated left internal carotid artery (ICA) occlusion with collateral circulation through the ophthalmic artery. Visual evoked potentials (VEPs) revealed a prechiasmal disturbance of the optic pathway of the left side. The patient had carotid endarterectomy of the left ICA, and his visual disturbance has gradually improved. Ocular symptoms due to ICA ischemia are commonly transient visual loss with dark background known as amaurosis fugax. Neovascular glaucoma is sometimes complicated with carotid artery occlusion. However, photopsia associated with carotid artery occlusion is rare. Photopsia mimics scintillating scotomata, but the latter precedes migraine and is biocular and homonymous, ascribable to spreading depression from the occipital lobe. Retinal or prechiasmal optic pathway might be influenced by poor circulation of the ophthalmic artery. In addition, disturbance of light adaptation due to retinal hypoperfusion may be possible reason. Neovascular glaucoma is intractable, once developed. Therefore, atypical scintillating visual disturbance must be recognized as a sign of carotid artery insufficiency and supervened glaucoma to prevent it.

[A case of chronic progressive radiation myelopathy successfully treated with corticosteroid].

One patient who underwent radiation therapy for laryngeal cancer two years earlier developed chronic progressive radiation myelopathy and exhibited localized swelling of the cervical spinal cord at the C4 level and resultant blocking of the subarachnoid space on myelography and CT myelography. The condition responded markedly to the administration of corticosteroid except for persisting mild spasticity and sensory disturbances. On myelography and CT myelography half a year later, the cervical spinal cord showed no swelling. The corticosteroid therapy is considered to be useful for radiation myelopathy.

[A case of acute motor sensory axonal polyneuropathy after Haemophilus influenzae infection].

A 47-year-old woman developed consciousness disturbance, and experienced hallucinations while traveling abroad, and then went into critical condition. She was placed in the critical care unit, and had flaccid tetraparesis requiring mechanical ventilation. Haemophilus influenzae was cultured from the sputum. The level of protein of the cerebrospinal fluid was elevated to 114 mg/dl, nerve conduction study showed findings of pure axonal damage, and the sural nerve biopsy revealed severe axonal degeneration. She improved gradually by plasma exchange. The diagnosis of acute motor sensory axonal polyneuropathy (AMSAN) based on autoimmune mechanism was made. We speculate that H. influenzae infection may have elicited AMSAN in this case.

[Study on the concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the lumbar cerebrospinal fluid (CSF) in neurological diseases].

Experimental evidence has shown that the amount of 5-HIAA in the CSF reflects the metabolism of serotonin in the brain if this metabolite is eliminated from the brain and flows into the CSF at a constant rate. We studied the concentration of 5-HIAA in the lumbar CSF in several neurological diseases to elucidate the alteration in abnormalities of serotonin metabolism. The concentration of 5-HIAA in the CSF was measured in 94 patients with cerebral infarction, 30 with vascular dementia, 25 with dementia of the Alzheimer type, 28 with Parkinson's disease and 6 with hypoxic encephalopathy. Patients with cerebral infarction were classified into 24 with a solitary cerebral infarct and 70 with multiple cerebral infarcts. Patients with Parkinson's disease were subdivided into 12 with various psychiatric symptoms including depressive state, hallucination and/or intellectual impairment and 16 without psychiatric symptoms. Patients with hypoxic encephalopathy consisted of 5 with apallic syndrome and one patient with Lance-Adams syndrome. The concentration of 5-HIAA in solitary cerebral infarct, multiple cerebral infarcts and vascular dementia did not exhibit a significant difference from that in control cases (54.6 +/- 23.1 ng/ml). But patients with dementia of the Alzheimer type (34.5 +/- 10.9, p less than 0.001) showed a significantly lower concentration. This fact seems to reflect the pathological finding that the number of large neurons is decreased and neurofibrillary tangles are increased in the nucleus raphe dorsalis of patients with Alzheimer type dementia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Secondary parkinsonism following midbrain hemorrhage].

We report a patient who developed right sided cogwheel rigidity and resting tremor after left midbrain hemorrhage. Brain magnetic resonance imaging (MRI) showed left midbrain old hemorrhage including substantia nigra. I-123 iodoamphetamine single photon emission computed tomography (IMP-SPECT) images showed reduced radioisotope (RI)-uptake in the left striatum, thalamus and frontal lobe. Our report shows that focal midbrain lesion can produce parkinsonism.

[A case of adult-onset neurenteric cyst presenting as chronic progressive muscular atrophy in lower legs].

A 50-year-old man was admitted, because of motor weakness of the lower limbs, dysesthesia of the left lower extremity, and anuresis. He had an episode of pain in his gluteal region 17 years ago, and then, no abnormalities were detected including myelography in a hospital, followed by slowly progressive muscular atrophy of his lower legs. At 50 years of age, dysuria appeared. He was diagnosed as having neurogenic bladder by urologists, and was admitted to our hospital. On admission, abnormal neurologic findings included: severe muscular atrophy in his lower legs, pes cavus, dysesthesia at the left S1 level, and autonomic bladder. Magnetic resonance imaging (MRI) showed mass lesion involving lower conus and cauda equina. After resection, pathological study revealed the mass was a neurenteric cyst. It is said that the neurenteric cyst causes an asymmetrical and sequential loss of specific neurological functions, with a subsequent return of these functions in the reverse order. That mechanism is not clear. However, in our case, the course of the illness was slowly progressive. We speculate that, because of the cyst's adhesion to cauda equina and perforation through the cyst by a nerve root, the cyst was fixed and caused slowly progressive neurological deficits in proportion to increase of the cyst's size. Our report suggests that a neurenteric cyst, involving the lower conus and cauda equina, can produce severe muscular atrophy in the lower legs.

[Persistent cerebellar ataxia following typhoid fever].

We report a patient who developed acute cerebellar ataxia, delirium, disseminated intravascular coagulation (DIC), and acute renal failure following typhoid fever. After treatment his general conditions improved except for cerebellar ataxia. Brain magnetic resonance imaging (MRI), before and after intravenous gadolinium administration, showed slight atrophy of the cerebellar vermis. 1-123 iodoamphetamine single photon emission computed tomography (IMP-SPECT) images showed markedly reduced radioisotope (RI) uptake in the cerebellum, and strongly implicated dysfunction of the cerebellum. Our report suggests that severe typhoid fever can produce persistent cerebellar dysfunction.